An Approach to Pyrrolidine-Containing Sphingomimetics Based on L-Tartaric Acid Chiron

A short synthetic approach to constructing pyrrolidine-containing sphingolipid-like derivatives has been accomplished. The cornerstone feature of the synthesis was a [3,3]-heterosigmatropic rearrangement of an imidate derived from l-tartaric acid chiron, which completed the core motif of the target sphingomimetics carrying three consecutive stereocentres and a terminal vinyl. A late-stage olefin cross metathesis reaction installed an alkyl side chain with the flexibility for analogue construction. The results obtained from biological screening have completed the structure-activity relationships in a series of eight prepared stereoisomeric C-alkyl pyrrolidinediols and elucidated the role of the stereochemistry on the heterocyclic skeleton towards the studied anticancer profile.